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首页> 外文期刊>Molecular cell >A Role for the Mitochondrial Pyruvate Carrier as a Repressor of the Warburg Effect and Colon Cancer Cell Growth
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A Role for the Mitochondrial Pyruvate Carrier as a Repressor of the Warburg Effect and Colon Cancer Cell Growth

机译：线粒体丙酮酸载体作为Warburg效应和结肠癌细胞生长的阻遏物的作用。

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摘要

Cancer cells are typically subject to profound metabolic alterations, including the Warburg effect wherein cancer cells oxidize a decreased fraction of the pyruvate generated from glycolysis. We show herein that the mitochondrial pyruvate carrier (MPC), composed of the products of the MPC1 and MPC2 genes, modulates fractional pyruvate oxidation. MPC1 is deleted or underexpressed in multiple cancers and correlates with poor prognosis. Cancer cells re-expressing MPC1 and MPC2 display increased mitochondrial pyruvate oxidation, with no changes in cell growth in adherent culture. MPC re-expression exerted profound effects in anchorage-independent growth conditions, however, including impaired colony formation in soft agar, spheroid formation, and xenograft growth. We also observed a decrease in markers of sternness and traced the growth effects of MPC expression to the stem cell compartment. We propose that reduced MPC activity is an important aspect of cancer metabolism, perhaps through altering the maintenance and fate of stem cells.
机译：癌细胞通常会发生深刻的代谢变化，包括Warburg效应，其中癌细胞会氧化糖酵解产生的丙酮酸的减少部分。我们在这里显示，由MPC1和MPC2基因的产物组成的线粒体丙酮酸载体（MPC）调节丙酮酸的部分氧化。 MPC1在多种癌症中缺失或表达不足，与不良预后相关。重新表达MPC1和MPC2的癌细胞显示线粒体丙酮酸氧化增加，在贴壁培养中细胞生长没有变化。 MPC重新表达在不依赖锚固的生长条件下产生了深远的影响，但包括软琼脂中菌落形成受损，球体形成和异种移植物生长。我们还观察到了严厉性标志物的减少，并追踪了MPC表达对干细胞区室的生长作用。我们提出降低MPC活性是癌症代谢的重要方面，也许是通过改变干细胞的维持和命运。

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